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1,N6-Ethenoadenine: From Molecular to Biological Consequences
- Source :
- Chemical Research in Toxicology. 33:2688-2698
- Publication Year :
- 2020
- Publisher :
- American Chemical Society (ACS), 2020.
-
Abstract
- Genomic DNA is chemically reactive and therefore susceptible to damage by many exogenous and endogenous sources. Lesions produced from these damaging events can have various mutagenic and genotoxic consequences. This Perspective follows the journey of one particular lesion, 1,N6-ethenoadenine (eA), from its formation to replication and repair, and its role in cancerous tissues and inflammatory diseases. eA is generated by the reaction of adenine (A) with vinyl chloride or lipid peroxidation products. We present the miscoding properties of eA with an emphasis on how bacterial and mammalian cells can process lesions differently, leading to varied mutational spectra. But with information from these assays, we can better understand how the miscoding properties of eA lead to biological consequences and how genomic stability can be maintained via DNA repair mechanisms. We discuss how base excision repair (BER) and direct reversal repair (DRR) can minimize the biological consequences of eA lesions. Kinetic parameters of glycosylases and AlkB family enzymes are described, along with a discussion of the relative contributions of the BER and DRR pathways in the repair of eA. Because eukaryotic DNA is packaged in chromatin, we also discuss the impact of this packaging on BER and DRR, specifically in regards to repair of eA. Studying DNA lesions like eA in this context, from origin to biological implications, can provide crucial information to better understand prevention of mutagenesis and cancer.
Details
- ISSN :
- 15205010 and 0893228X
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Chemical Research in Toxicology
- Accession number :
- edsair.doi...........18b8014021281867e69a59dd04b42995